Osteoporosis is a systemic disease with bone fragility accompanied by idiopathic dysregulation of bone remodeling which consists in a balance between bone resorption and bone formation. Dysregulation of bone remodeling in osteoporosis results from the enhancement of bone resorption and/or the suppression of bone formation, which occurred systemically. These are independent of presence of local inflammation.
Enhancement of bone resorption is induced by progression of osteoclastogenesis or activation of osteoclasts. Factors promoting osteoclastogenesis such as receptor activator of NF-κB ligand (RANKL) are well known. RANKL promotes osteoclastogenesis and osteoclast activation leading to bone resorption through binding to its receptor, RANK. In addition, osteoprotegerin (OPG) is known as a physiological inhibitor for RANKL and RANK. It has been established that RANK/RANKL/OPG system exerts the central significance on regulation of bone mass (Non-Patent Document 1).
It has been reported that the benzophenone derivatives described in this application have the AP-1 inhibitory effect and are prominent therapeutic agents for autoimmune diseases (Patent Document 1).
However, it has been absolutely unknown that these agents have suppressive effect on RANKL production, suppressive effect on OPG reduction and inhibitory effects on differentiation/activation of osteoclasts.
[Patent Document 1]
    International publication WO03/042150 pamphlet[Non-Patent Document 1]    Cancer Biology and Therapy, 2006, Vol. 5, page 1078-1081.